Trial record 13 of 31 for:    " July 01, 2012":" July 31, 2012"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

Daily Trimethoprim-sulfamethoxazole or Weekly Chloroquine Among Adults on ART in Blantyre, Malawi (TSCQ)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by University of Maryland
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Miriam Laufer, University of Maryland
ClinicalTrials.gov Identifier:
NCT01650558
First received: July 6, 2012
Last updated: December 10, 2012
Last verified: December 2012
  Purpose

The purpose of this study is to determine if there is a benefit to taking trimethoprim-sulfamethoxazole (TS) as prophylaxis among HIV positive adults who have viral load suppression and a good clinical response on anti-retroviral therapy (ART). If there is a benefit, then is it due to antimalarial or antibacterial properties.

The investigators hypothesize that there will be a long-term benefit on survival and disease control in the context of prophylaxis and that the benefit will largely be attributed to prevention of malaria. The main study hypothesis is that 1)TS and chloroquine (CQ) will decrease the rates of morbidity and mortality among adults after 6 or more months of ART and 2) CQ prophylaxis will be associated with more prolonged viral suppression and higher CD4 cell counts than TS prophylaxis or no prophylaxis.


Condition Intervention
HIV
Drug: Standard of Care prophylaxis
Drug: Chloroquine (CQ) prophylaxis

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Randomized, Open-label Controlled Trial of Daily Trimethoprim-sulfamethoxazole or Weekly Chloroquine Among Adults on Anti-retroviral Therapy in Blantyre, Malawi

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • Severe events [ Time Frame: 2 to 3.5 years ] [ Designated as safety issue: No ]
    Incidence of severe events (composite of death and WHO stage 3 and 4 illness)


Secondary Outcome Measures:
  • HIV viral load [ Time Frame: Every 6 months for 2-3.5 years ] [ Designated as safety issue: No ]
    Incidence of detectable viral load (>400 copies/ml)

  • CD4 cell count [ Time Frame: Every 6 months for 2-3.5 years ] [ Designated as safety issue: No ]
    CD4 cell counts compared among those on prophylaxis with TS or CQ versus no prophylaxis

  • WHO HIV stage 2, 3, 4 illness [ Time Frame: 2 to 3.5 years ] [ Designated as safety issue: No ]
    Incidence of any WHO HIV stage 2, 3, or 4 illness

  • Bacterial infections and malaria [ Time Frame: 2 to 3.5 years ] [ Designated as safety issue: No ]
    Incidence of bacterial infections and malaria

  • Adverse events greater than or equal to Grade 3 that are related to the study product [ Time Frame: 2 to 3.5 years ] [ Designated as safety issue: Yes ]
    Occurrence of adverse events that are greater than or equal to Grade 3 that require discontinuation of TS or CQ prophylaxis


Other Outcome Measures:
  • Bacterial or malaria infection with CQ or TS resistant organism [ Time Frame: 2 to 3.5 years ] [ Designated as safety issue: No ]
    Occurrence of bacterial or malaria infection with CQ or TS resistant organism

  • Clinical and parasitological response to antimalarial therapy [ Time Frame: 2 to 3.5 years ] [ Designated as safety issue: No ]
    Clinical and parasitological response to antimalarial therapy in cases of uncomplicated malaria


Estimated Enrollment: 900
Study Start Date: November 2012
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard of Care Prophylaxis (TS)
Standard of care prophylaxis with daily trimethoprim sulfamethoxazole (TS).
Drug: Standard of Care prophylaxis
Daily trimethoprim sulfamethoxazole
Other Names:
  • Bactrim
  • Co-trimoxazole
Experimental: Chloroquine (CQ) prophylaxis
Discontinuation of standard of care TS prophylaxis and starting weekly chloroquine prophylaxis
Drug: Chloroquine (CQ) prophylaxis
Discontinue standard of care and start weekly CQ.
Other Name: Aralen
No Intervention: Discontinuation of standard of care
Control arm - Discontinuation of standard of care trimethoprim sulfamethoxazole.

Detailed Description:

This is a randomized, controlled, open-label, phase III trial of standard of care TS prophylaxis and CQ prophylaxis compared to no prophylaxis in adults receiving ART. Adults who have been receiving ART for at least six months with a good clinical response and provide informed consent and fulfill the eligibility criteria will be randomized to one of three arms: (1) to continue standard of care trimethoprim-sulfamethoxazole (TS) prophylaxis, (2) discontinue standard of care TS prophylaxis and begin weekly CQ prophylaxis or (3) discontinue standard of care TS prophylaxis. Participants will be asked to return to the research clinic every four weeks and any time they are ill to facilitate both active and passive follow-up of the study endpoints. Participation will last for 24 to approximately 42 months. Participants who develop a WHO clinical stage 3 or 4 illness (see Appendix A for a complete listing), experience a sustained decline in their CD4 count below 200 cells/mm3, or who experience ART failure will be placed on standard of care TS prophylaxis. Those with confirmed ART failure will be evaluated for second-line therapy according to the Malawi Ministry of Health guidelines.

The study population will include 900 Malawian adults aged 18 years or older living with HIV in or near Blantyre, Malawi, Central Africa who have been receiving antiretroviral therapy for at least 6 months with good clinical response to ART, have an undetectable HIV viral load and a CD4 count >250/mm3. Participants must intend to stay in Blantyre for the entire study period.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 years or older
  • Documented HIV-1 infection
  • Initiation of ART through a government-sponsored ART program at least six months prior
  • Undetectable HIV viral load (< 400 copies/mL)
  • CD4 count > 250/mm3
  • TS prophylaxis prescribed for at least the previous 2 months
  • Intention to remain in the study area until the end of the study period
  • Informed consent from participant
  • Female study volunteers of reproductive potential must have a negative serum urine pregnancy test performed within 20 days before randomization.
  • Female study volunteers of reproductive potential who participate in sexual activity that could lead to pregnancy must use contraception (male or female condoms, diaphragm or cervical cap with spermicide, intrauterine device, or hormone-based contraceptive) while receiving their assigned study drug and for one month after stopping the medications.

Exclusion Criteria:

  • Severe acute illness (defined as requiring hospitalization at the time of screening or other conditions such as laboratory abnormalities as determined by the investigators)
  • Chronic treatment (requiring therapy for > 14 days) or secondary prophylaxis (for toxoplasmosis, Pneumocystis pneumonia, or tuberculosis for example) with any drug with antimalarial or antibacterial activity
  • History of hypersensitivity to antifolate drugs or CQ
  • Laboratory exclusion criteria
  • Hemoglobin < 8.0 gm/dL
  • Platelet count < 50,000/mm3
  • Absolute granulocyte count < 500/mm3
  • Serum alanine aminotransferase (ALT) concentration > 210 U/L for men, >160 U/L for women
  • Serum creatinine concentration > 3.3mg/dl (291.7µmol/L) for men, and > 2.7mg/dl (238.7µmol/L) for women)
  • History of visual field or retinal changes
  • History of preexisting auditory damage
  • History of porphyria
  • History of psoriasis
  • History of liver disease
  • History of seizure disorder
  • History of glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • History of ECG and cardiac conduction abnormality or cardiomyopathy
  • History of myopathy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01650558

Locations
Malawi
Blantyre Malaria Project Research Clinic Recruiting
Blantyre, Malawi
Contact: Randy Mungwira, MD    +265-1-875-021    rgmungwira@gmail.com   
Contact: Jane Mallewa, MD    +265 1-874-628    janemallewa@yahoo.com   
Sub-Investigator: Joep JG van Oosterhout, MD         
Sub-Investigator: Matthew B Laurens, MD, MPH         
Sub-Investigator: Terrie E Taylor, DO         
Sponsors and Collaborators
University of Maryland
Investigators
Principal Investigator: Miriam K Laufer, MD, MPH University of Maryland, Baltimore County
  More Information

No publications provided

Responsible Party: Miriam Laufer, Associate Professor of Pediatrics, University of Maryland
ClinicalTrials.gov Identifier: NCT01650558     History of Changes
Other Study ID Numbers: HP-00043360; DAIDS ES-10822, U01AI089342-01A1
Study First Received: July 6, 2012
Last Updated: December 10, 2012
Health Authority: United States: Institutional Review Board
United States: Data and Safety Monitoring Board
Malawi: College of Medicine Research and Ethics Committee

Keywords provided by University of Maryland:
Malaria
HIV
Prophylaxis
Antiretroviral therapy

Additional relevant MeSH terms:
Chloroquine
Chloroquine diphosphate
Trimethoprim
Trimethoprim-Sulfamethoxazole Combination
Sulfamethoxazole
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Filaricides
Antinematodal Agents
Anthelmintics
Central Nervous System Agents
Anti-Infective Agents, Urinary
Renal Agents
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2014